Study On The Trifluoromethylthio And Amidation Of 2-azidoarylalkynone

The introduction of a fluorine-containing functional group at a specific site of an organic molecule can effectively change the physical,academic and biological activities of the molecule.Therefore,the fluorine-containing functional group is often used for structural modification and modification of functional materials of pharmaceutical chemicals and agrochemicals.Among many groups containing fluorine,trifluoromethylthio（SCF₃）occupies a very important position due to its strong electron withdrawing effect and high lipophilicity.Compared with the parent molecule,the membrane permeability and absorption rate of the molecule with the introduction of trifluoromethylthio group are greatly improved.At present,more and more drug molecules containing trifluoromethylthio groups have been developed,such as:Tiflorex,Losartan analogue and Toltrazuril all showed good pharmacological activity.In addition,amide bonds,the most important functional groups in nature,are the key chemical linkages of proteins.They constitute a general part of organic chemistry synthesis,and are important and ubiquitous structural sequences in currently discovered drugs and polymer materials.Therefore,the amidation reaction based on the construction of amide bonds is becoming more and more important,and it has always been one of the hot spots in the field of synthetic chemistry.This thesis first systematically describes the research progress of electrophilic,nucleophilic and free radical trifluoromethylthiolation reactions and the construction of amide bonds.On this basis,we designed and explored the trifluoromethylthio-radical tandem cyclization reaction and the acetamidation of acetonitrile catalyzed by aluminum triflate with 2-azidoarylalkynone as the substrate.The main contents of the paper are as follows:In Chapter 1,starting from the significance of the trifluoromethylthio reaction and amidation reaction,a more comprehensive summary of the reactions involved in various electrophilic,nucleophilic and free radical trifluoromethylthio reagents.Amines and carboxylic acids,esters,alcohols,aldehydes,ketones directly build amide bonds based on the amidation reaction.Then elaborated the background of this thesis and the basis for selecting the topic.Chapter 2 introduces the strong oxidation system in which 2-azidoarylalkynone is used as the substrate,Mainly.Ag SCF₃ is used as the source of trifluoromethyl sulfide,and Na₂S₂O₈ exists.A free radical trifluoromethylthio-tandem cyclization reaction initiated by the addition of a carbon-carbon triple bond occurs.This strategy was constructed through the simultaneous construction of C（sp²）-SCF₃ bonds and C-N bonds to synthesize a series of SCF₃-substituted 4（1H）-quinolones and their derivatives.This strategy has the advantages of simple operation and good functional group tolerance.The study on the acetamidation tandem cyclization reaction of 2-azidoarylalkynone promoted by the hydrolysis of acetonitrile catalyzed by aluminum trifluorosulfinate is summarized in Chapter 3.Based on this strategy,a series of acetylamino-substituted3（1H）-indolinone derivatives were synthesized.This reaction realizes the simultaneous construction of C（sp²）-N bond and C（sp³）-N bond in a one-step reaction process.The hydrogen spectrum,carbon spectrum and high resolution have all tested and verified the structure of the above compounds,and some representative compounds have also undergone X-Ray experiments to confirm their structures.